Publication Date:
2015-02-24
Description:
Mutations in sunlight-induced melanoma arise from cyclobutane pyrimidine dimers (CPDs), DNA photoproducts that are typically created picoseconds after an ultraviolet (UV) photon is absorbed at thymine or cytosine. We found that in melanocytes, CPDs are generated for 〉3 hours after exposure to UVA, a major component of the radiation in sunlight and in tanning beds. These "dark CPDs" constitute the majority of CPDs and include the cytosine-containing CPDs that initiate UV-signature C--〉T mutations. Dark CPDs arise when UV-induced reactive oxygen and nitrogen species combine to excite an electron in fragments of the pigment melanin. This creates a quantum triplet state that has the energy of a UV photon but induces CPDs by energy transfer to DNA in a radiation-independent manner. Melanin may thus be carcinogenic as well as protective against cancer. These findings also validate the long-standing suggestion that chemically generated excited electronic states are relevant to mammalian biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432913/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432913/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Premi, Sanjay -- Wallisch, Silvia -- Mano, Camila M -- Weiner, Adam B -- Bacchiocchi, Antonella -- Wakamatsu, Kazumasa -- Bechara, Etelvino J H -- Halaban, Ruth -- Douki, Thierry -- Brash, Douglas E -- 2 P50 CA121974/CA/NCI NIH HHS/ -- P30 DK034989/DK/NIDDK NIH HHS/ -- P30 DK34989/DK/NIDDK NIH HHS/ -- P50 CA121974/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):842-7. doi: 10.1126/science.1256022.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA. ; Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA. Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao Paulo 05513-970 SP, Brazil. ; Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520, USA. ; Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Aichi 470-1192, Japan. ; Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao Paulo 05513-970 SP, Brazil. Departamento de Ciencias Exatas e da Terra, Universidade Federal de Sao Paulo, Diadema, Sao Paulo 09972-270 SP, Brazil. ; Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520, USA. Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA. ; INAC/LCIB UMR-E3 CEA-UJF/Commissariat a l'Energie Atomique (CEA), 38054 Grenoble Cedex 9, France. ; Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA. Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA. douglas.brash@yale.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700512" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cells, Cultured
;
Cytosine/metabolism
;
DNA/chemistry/genetics/*radiation effects
;
DNA Damage/*genetics
;
Energy Transfer
;
Humans
;
Melanins/chemistry/*metabolism
;
Melanocytes/metabolism/*radiation effects
;
Melanoma/*genetics
;
Mice
;
Mice, Inbred C57BL
;
Mutagenesis
;
Mutation
;
Neoplasms, Radiation-Induced/*genetics
;
Photons
;
Pyrimidine Dimers/*metabolism
;
Receptor, Melanocortin, Type 1/genetics
;
Skin Neoplasms/*genetics
;
Sunlight/adverse effects
;
Thymine/metabolism
;
Ultraviolet Rays
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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